1. Field of the Invention
The present invention relates to a novel halogenating agent, preparation process and use of the agent.
2. Related Art of the Invention
Many processes have been conventionally known related to the halogenating reaction of organic compounds. Halogenating agents which can be generally used are hydrogen halogenide, halogen-phosphorus compounds, halogen-sulfur compounds and halogen simple substances. However, these substances have high corrosivity and toxicity, and many of them require specific equipment and technique for handling these agents. Consequently, in view of ease handling, safety and reactivity, development research on various halogenating agents has been continued still now. Particularly in the preparation of fluorine compounds, fluorinating agents are generally very dangerous. Thus, specific equipment and techniques having a further high level as compared with other halogenating reaction are required and also lead to higher load in economy.
Fluorinating agents which have been conventionally used for a fluorinating reaction are fluorine, hydrogen fluoride, and tetrafluorinated sulfur. However, these conventional fluorinating agents are difficult to handle due to toxicity, corrosivity and danger of explosion in the reaction step and require specific equipment and techniques. Further, poor selectivity of a fluorine bonding in the reaction is also a problem. On the other hand, development of new products utilizing fluorine compounds has been carried out in functional materials, physiologically active substances and other various fields. In recent years, various fluorinating agents have been developed to cope with these demands.
For example, as a representative agent which has been developed for a fluorinating agent of a hydroxyl group, carboxyl group and other oxygen containing functional groups, U.S. Pat. No. 3,976,691 has disclosed DAST (diethylaminosulfurtrifluoride). DAST has been introduced as an excellent fluorinating agent of oxygen in an alcoholic hydroxyl group or a carbonyl group. However, in the preparation of DAST, highly dangerous tetrafluorinated sulfur is reacted with dimethylaminotrimethylsilane at a low temperature of xe2x88x9278xc2x0 C. to xe2x88x9260xc2x0 C. Thus, a specific manufacturing facility is required. As to safety, explosion has been reported on the production and use of DAST [J. Fluorine Chem., 42 137 (1989)].
Further, WO 96/04297 has described that tetraalkyl-fluoroform-amidinium=salt is an excellent fluorinating agent of a carboxyl group. However, no description has been found on the fluorinating reaction of other functional groups. The application has described that halogen ions are included as a counter ion of tetraalkyl-fluoroformamidinium salt. However, in practice, PF6xe2x88x92 is an only one example shown as a counter ion. Therefore, the present inventors have prepared 1,3-dimethyl-2-fluoroimidazolinium=hexafluorophosphate in accordance with the process of WO 96/04297, and used for the replacement of individual hydroxyl group on benzoic acid, benzyl alcohol and n-octanol into fluorine. As a result, benzoyl fluoride has been formed from benzoic acid. However, formation of fluorine compounds could not be observed in the fluorinating reaction of benzyl alcohol and n-octanol. Japanese Laid-Open Patent HEI 4-308538 has disclosed a halogenating reaction of primary alcohol by using a haloiminium salt as a halogenating agent. Japanese Laid-Open Patent HEI 9-67299 has described a halogenation reaction of carboxylic acid. Both literatures have described that the counter ion of haloiminium salt includes a halogen ion. However, in practice, the counter ion is an example of Clxe2x88x92 alone. Quite no description is found on a fluorinating agent in particular.
Further, DE 2627986 and Japanese Laid-Open Patent SHO 52-156810 have described use of bis-dialkylaminodifluoromethane as a reaction catalyst in the preparation of perfluoroalkoxypropionyl fluoride. However, no description has been found on a fluorinating agent. The preparation is carried out by reacting hexafluoropropene oxide with tetraalkylurea, and the source of fluorine is expensive and difficult to handle.
As a mentioned above, the fluorinating agent of an oxygen containing functional group has not yet satisfactorily developed for use in industry in view of preparation process, selectivity, yield and economy.
One object of the invention is to provide a halogenating agent of an organic compound, a fluorinating agent in particular, which eliminates the above problems of the prior art and can be prepared by a technically and economically improved process in industry and is excellent in reactivity and economy, to provide a preparation process of the halogenating agent, and to provide a preparation process of compounds obtained by halogenating, fluorinating in particular, various organic compounds with the agent.
As a result of an intensive investigation in order to solve the above objects, the present inventors have found that the compound represented by the formula (1): 
wherein R1 to R4 is a substituted or unsubstituted, saturated or unsaturated alkyl group or a substituted or unsubstituted aryl group and can be the same or different; R1 and R2 or R3 and R4 can bond to form a ring including a nitrogen atom or a nitrogen atom and other hetero atoms; or R1 and R3 can bond to form a ring including a nitrogen atom or a nitrogen atom and other hetero atoms, is a novel excellent fluorinating agent which is selective for a hydroxyl group, carboxyl group, formyl group, ketone group and other oxygen containing functional groups, and further found that application to the fluorinating reaction requires no specific equipment and technique and can be carried out in extreme safety and with ease.
Further, they have found that the compound represented by the formula (1) can be obtained by way of a halogen exchange reaction of the compound represented by the formula (14): 
wherein X2 and X3 are chlorine or bromine atoms and can be the same or different; R1 to R4 is a substituted or unsubstituted, saturated or unsaturated alkyl group or a substituted or unsubstituted aryl group and can be the same or different ; R1 and R2 or R3 and R4 can bond to form a ring including a nitrogen atom or a nitrogen atom and other hetero atoms; or R1and R3 can bond to form a ring including a nitrogen atom or a nitrogen atom and other hetero atoms, and thus no specific equipment and technique are required and can be safely manufactured in industry
They have also found that the fluorinating agent represented by the formula (1) can be recovered after fluorinating reaction in the form of urea and can be reused in economy for the raw material of the compound represented by the formula (14).
Further, they have also found that the compound represented by the formula (15): 
wherein X4 and X5 are halogen atoms and can be the same or different except that both of X4 and X5 are fluorine atoms, chlorine atoms or bromine atoms; R1 to R4 is a substituted or unsubstituted, saturated or unsaturated alkyl group or a substituted or unsubstituted aryl group and can be the same or different; R1and R2 or R3 and R4 can bond to form a ring including a nitrogen atom or a nitrogen atom and other hetero atoms, is an excellent, novel halogenating agent which is selective for a hydroxyl group, carboxyl group, formyl group and other oxygen containing functional groups, and further found that application to the halogenation reaction requires no specific equipment and technique and can be carried out in extreme safety with ease.
That is, the aspect of the invention will be illustrated from (1) to (45) below.
(1) A fluorinating agent represented by the formula (1): 
wherein R1 to R4 is a substituted or unsubstituted, saturated or unsaturated alkyl group, saturated or unsaturated aryl group, and can be the same or different; R1 and R2 or R3 and R4 can bond to form a ring including a nitrogen atom or a nitrogen atom and other hetero atoms; or R1 and R3 can bond to form a ring including a nitrogen atom or a nitrogen atom and other hetero atoms.
(2) A fluorinating agent according to the above (1) wherein the fluorinating agent represented by the formula (1) is represented by the formula (2): 
wherein a is an integer of 2 or 3, R5 and R6 are substituted or unsubstituted, saturated or unsaturated lower alkyl groups having 1 to 6 carbon atoms and can be the same or different.
(3) A fluorinating agent according to the above (2) wherein the fluorinating agent represented by the formula (2) is 2,2-difluoro-1,3-dimethylimidazolidine represented by the formula (3): 
(4) A fluorinating agent according to the above (2) wherein the fluorinating agent represented by the formula (2) is 2,2-difluoro-1,3-di-n-butylimidazolidine represented by the formula (4): 
(5) A fluorinating agent according to the above (1) wherein the fluorinating agent represented by the formula (1) is represented by the formula(5): 
wherein R7 to R10 is a substituted or unsubstituted, saturated or unsaturated lower alkyl group having 1 to 6 carbon atoms, and can be the same or different; R7 and R8 or R9 and R10 can bond to form a ring including a nitrogen atom or a nitrogen atom and other hetero atoms; or R7 and R9 can bond to form a ring including a nitrogen atom or a nitrogen atom and other hetero atoms.
(6) A fluorinating agent according to the above (5) wherein the fluorinating agent represented by the formula (5) is bis-dimethylamino-difluoromethane represented by the formula (6): 
(7) A fluorinating agent according to the above (5) wherein the fluorinating agent represented by the formula (5) is bis-di-n-butylamino-difluoromethane represented by the formula (7): 
(8) A preparation process of a fluorine compound represented by the formula (8-1):
R11xe2x80x94Fxe2x80x83xe2x80x83(8-1)
wherein R11 is a substituted or unsubstituted alkyl group and can include an unsaturated group therein, comprising reacting a compound having an alcoholic hydroxyl group and represented by the formula (8):
R11xe2x80x94OHxe2x80x83xe2x80x83(8)
wherein R11 is the same as in the formula (8-1), with the above fluorinating agent represented by the formula (1).
(9) A preparation process of a fluorine compound represented by the formula (9-1): 
wherein Y1 is an electrophilic substituent, b is an integer of 1 to 5, c is an integer of 1 to 5, and b+cxe2x89xa66, comprising reacting a compound of phenol species or thiophenol species represented by the formula (9): 
wherein Q is an oxygen or a sulfur atom, and Y1, b and c are the same as in the formula (9-1), with the above fluorinating agent represented by the formula (1).
(10) A preparation process of a fluorine compound represented by the formula (10-1):
R12xe2x80x94CHF2xe2x80x83xe2x80x83(10-1)
wherein R12 is a substituted or unsubstituted, saturated or unsaturated alkyl group, or a substituted or unsubstituted aryl group, comprising reacting an aldehyde compound represented by the formula (10):
R12xe2x80x94CHOxe2x80x83xe2x80x83(10)
wherein R12 is the same as in the formula (10-1), with the above fluorinating agent represented by the formula (1).
(11) A preparation process of a fluorine compound represented by the formula (11-1): 
wherein R13 and R14 are a substituted or unsubstituted alkyl group or a substituted or unsubstituted aryl group and can be the same or different; the alkyl group can include unsaturated group, and R13 and R14 can bond to form a ring, comprising reacting a ketone compound represented by the formula (11): 
wherein R13 and R14 are the same as in the formula (11-1), with the above fluorinating agent represented by the formula (1).
(12) A preparation process of an acid fluoride represented by the formula (12-1):
R12xe2x80x94COFxe2x80x83xe2x80x83(12-1)
wherein R15 is a substituted or unsubstituted, saturated or unsaturated alkyl group or a substituted or unsubstituted aryl group, comprising reacting a carboxyl compound represented by the formula (12):
R15xe2x80x94COOHxe2x80x83xe2x80x83(12)
wherein R15 is the same as in the formula (12-1), with the above fluorinating agent represented by the formula (1).
(13) A preparation process of a fluorine compound represented by the formula (13-1): 
wherein Y1 is an electrophilic substituent, b and d are integers of 1 to 5, and b+dxe2x89xa66, comprising reacting an aromatic compound comprised of a halogen atom except fluorine and represented by the formula (13): 
wherein X1 is a halogen atom except fluorine, and Y1, b and d are the same as in the formula (13-1), comprising reacting with the above fluorinating agent represented by the formula (1).
(14) A preparation process of a fluorine containing olefinic compound represented by the formula (25) 
wherein R15 to R17 are a hydrogen atom or a lower alkyl group having 1 to 3 carbon atoms and can be the same or different; and Z is xe2x80x94(Y)nxe2x80x94CHF2xe2x80x94(Y)nxe2x80x94CH2F or xe2x80x94COxe2x80x94Oxe2x80x94(Y)nxe2x80x94CH2F, wherein Y is xe2x80x94CH2xe2x80x94 and n is 0 or an integer of 1 to 5, comprises reacting a fluorinating agent represented by the formula (1) with olefinic compounds represented by the formula (24) 
wherein R15 to R17 are a hydrogen atom or a lower alkyl group having 1 to 3 carbon atoms and can be the same or different; and X is xe2x80x94(Y)nxe2x80x94CHO, xe2x80x94(Y)nxe2x80x94CH2OH, or xe2x80x94COxe2x80x94Oxe2x80x94(Y)nxe2x80x94CH2OH, wherein Y is xe2x80x94CH2xe2x80x94 and n is 0 or an integer of 1 to 5.
(15) A process according to one of the above 8 to 14 wherein the fluorinating agent is represented by the formula (2).
(16) A compound represented by the formula (2): 
wherein a is an integer of 2 or 3, R5 and R6 are a substituted or unsubstituted, saturated or unsaturated lower alkyl group having 1 to 6 carbon atoms and can be the same or different.
(17) A compound wherein the formula (2) is 2,2-difluoro-1,3-dimethylimidazolidine represented by the formula (3): 
(18) A compound wherein the formula (2) is 2,2-difluoro-1,3-di-n-butylimidazolidine represented by the formula (4): 
(19) A compound wherein the formula (5) is bis-di-n-butylamino-difluoromethane represented by the formula (7): 
(20) A preparation process of a fluorinating agent represented by the formula (1) in the above (1) comprising carrying out a halogen exchange reaction of a compound represented by the formula (14): 
wherein X2 and X3 are a chlorine or a bromine atom, R1 to R4 are substituted or unsubstituted, saturated or unsaturated alkyl group, substituted or unsubstituted aryl group, and can be the same or different; R1 and R2 or R3 and R4 can bond to form a ring including a nitrogen atom or a nitrogen atom and other hetero atoms; or R1 and R3 can bond to form a ring including a nitrogen atom or a nitrogen atom and other hetero atoms, with an alkali metal salt of a fluorine atom in an inert solvent.
(21) A preparation process of a fluorinating agent of the above (1) comprising reacting a compound represented by the formula (14) with a half equivalent of sodium fluoride, separating by filtration, and successively reacting with potassium fluoride.
(22) A halogenating agent represented by the formula (15): 
wherein X4 and X5 are a halogen atom and can be the same or different except that both X4 and X5 are not fluorine atoms, chlorine atoms or bromine atoms; R1 to R4 are a substituted or unsubstituted, saturated or unsaturated alkyl group or a substituted or unsubstituted aryl group, and can be the same or different; R1 and R2 or R3 and R4 can bond to form a ring including a nitrogen atom or a nitrogen atom and other hetero atoms; or R1and R3 can bond to form a ring including a nitrogen atom or a nitrogen atom and other hetero atoms.
(23) A halogenating agent according to the above (22) wherein the halogenating agent represented by the formula (15) is represented by the formula (16): 
wherein X4 and X5 are a halogen atom and can be the same or different except that both X4 and X5 are not fluorine atoms, chlorine atoms or bromine atoms; a is an integer of 2 or 3, R5 and R6 are a substituted or unsubstituted, saturated or unsaturated lower alkyl group having 1 to 6 carbon atoms and can be the same or different.
(24) A halogenating agent according to the above (23) wherein the halogenating agent represented by the formula (16) is 2-halo-1,3-dimethylimidazolinium=halide represented by the formula (17): 
wherein X4 and X5 are a halogen atom and can be the same or different except that both X4 and X5 are not fluorine atoms, chlorine atoms or bromine atoms.
(25) A halogenating agent according to the above (23) wherein the halogenating agent represented by the formula (16) is 2-fluoro-1,3-dimethylimidazolinium=chloride represented by the formula (18): 
(26) A halogenating agent according to the above (23) wherein the halogenating agent represented by the formula (16) is 2-fluoro-1,3-dimethylimidazolinium=bromide represented by the formula (19): 
(27) A halogenating agent according to the above (23) wherein the halogenating agent represented by the formula (16) is 2-fluoro-1,3-dimethylimidazolinium=iodide represented by the formula (20): 
(28) A halogenating agent according to the above (23) wherein the halogenating agent represented by the formula (16) is 2-chloro-1,3-dimethylimidazolinium=bromide represented by the formula (21): 
(29) A halogenating agent according to the above (23) wherein the halogenating agent represented by the formula (16) is 2-chloro-1,3-dimethylimidazolinium=iodide represented by the formula (22): 
(30) A halogenating agent according to the above (23) wherein the halogenating agent represented by the formula (16) is 2-iodo-1,3-dimethylimidazolinium=iodide represented by the formula (23): 
(31) A preparation process of a halogenating agent represented by the above formula (15) according to the above (21) comprising carrying out a halogen exchange reaction of a compound represented by the formula (14): 
wherein X2 and X3 are a chlorine or bromine atom and R1 to R4 are the same as above, with an alkali metal salt of a fluorine atom, chlorine atom, bromine atom or iodine atom or a mixture thereof in an inert solvent.
(32) A preparation process of a halogen compound represented by the formula (8-2):
R11xe2x80x94X5xe2x80x83xe2x80x83(8-2)
wherein R11 is a substituted or unsubstituted alkyl group and can include an unsaturated group therein and X5 is a halogen atom, comprising reacting an alcoholic hydroxyl compound represented by the formula (8):
R11xe2x80x94OHxe2x80x83xe2x80x83(8)
wherein R11 is the same as in the formula (8-2), with the above halogenating agent represented by the formula (15): 
wherein X4, X5, and R1 to R4 are the same as above.
(33) A preparation process of an acid halogenide species represented by the formula (12-2):
R15xe2x80x94COX6xe2x80x83xe2x80x83(12-2)
wherein R15 is a substituted or unsubstituted, saturated or unsaturated alkyl group or substituted or unsubstituted aryl group and X6 is a halogen atom represented by X4 or X5 in the formula (15), comprising reacting a carboxylic acid compound represented by the formula (12):
R15xe2x80x94COOHxe2x80x83xe2x80x83(12)
wherein R15 is the same as in the formula (12-2), with a halogenating agent represented by the formula (15): 
wherein X4, X5 and R1 to R4 are the same as above.
(34) A preparation process of a fluorine compound represented by the formula (10-2):
R12xe2x80x94CH (X7)2xe2x80x83xe2x80x83(10-2)
wherein R12 is a substituted or unsubstituted, saturated or unsaturated alkyl group, or a substituted or unsubstituted aryl group, and X7 is a halogen atom represented by X4 or X5 in the formula (15) and two X7 can be the same or different, comprising reacting an aldehyde compound represented by the formula (10):
R12xe2x80x94CHOxe2x80x83xe2x80x83(10)
wherein R12 is the same as in the formula (10-2), with a halogenating agent represented by the formula (15): 
wherein X4, X5 and R1 to R4 are the same as above.
(35) A preparation process of a halogen compound according to one of the above 32 to 34 wherein the halogenating agent is represented by the formula (17).
(36) A compound represented by the formula (15): 
wherein X4 and X5 are a halogen atom and can be the same or different except that both X4 and X5 are not fluorine atoms, chlorine atoms or bromine atoms; R1 to R4 are a substituted or unsubstituted, saturated or unsaturated alkyl group or a substituted or unsubstituted aryl group and can be the same or different; R1 and R2 or R3 and R4 can bond to form a ring including a nitrogen atom or a nitrogen atom and other hetero atoms; or R1 and R3 can bond to form a ring including a nitrogen atom or a nitrogen atom and other hetero atoms.
(37) A compound represented by the formula (16): 
wherein X4 and X5 are same or different halogen atom except that both X4 and X5 are fluorine atom, chlorine atom or bromine atom, a is an integer of 2 or 3, R5 and R6 are a substituted or unsubstituted, saturated or unsaturated lower alkyl group having 1 to 6 carbon atoms and can be the same or different.
(38) A halogenating agent according to the above (22) wherein the halogenating agent is 2-halo-1,3-dimethylimidazolinium=halide represented by the formula (17): 
wherein X4, X5 are the same as above.
(39) A compound, 2-fluoro-1,3-dimethylimidazolinium=chloride represented by the formula (18): 
(40) A compound, 2-fluoro-1,3-dimethylimidazolinium=bromide represented by the formula (19): 
(41) A compound, 2-fluoro-1,3-dimethylimidazolinium=iodide represented by the formula (20): 
(42) A compound, 2-chloro-1,3-dimethylimidazolinium=bromide represented by the formula (21): 
(43) A compound, 2-chloro-1,3-dimethylimidazolinium=iodide represented by the formula (22): 
(44) A compound, 2-iodo-1,3-dimethylimidazolinium iodide represented by the formula (23): 
(45) A preparation process of a halogenating agent represented by the formula (15): 
wherein R1 to R4, X4 and X5 are the same as above, comprising carrying out a halogen exchange reaction of a compound represented by the formula (1): 
wherein R1 to R4 are the same as above, with an alkali metal salt of chlorine a chlorine, bromine or iodine atom in the presence of an inert solvent.
The halogenating agent of the invention, fluorinating agent in particular, is a fluorinating agent for a hydroxyl group, carboxyl group and other oxygen containing functional groups of a compound, can be handled with safety and ease, and has high selectivity. Preparation of the fluorinating agent of the invention requires no specific equipment and technique and can be carried out with economy. Further, a halogenating agent obtained by substituting other halogen atom for the fluorine atom can also be applied to the preparation of compounds having halogen other than fluorine.
The halogenating agent of the invention, fluorinating agent in particular, has eliminated problems of conventional techniques for the preparation of the agent itself in industry and exhibits excellent effects as a halogenating agent, fluorinating agent in particular, for organic compounds particularly having an oxygen containing functional group.